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Genetic and phenotypic landscape of the major histocompatibilty complex region in the Japanese population
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Genetic and phenotypic landscape of the major histocompatibilty complex region in the Japanese population
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Genetic and phenotypic landscape of the major histocompatibilty complex region in the Japanese population
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Journal Article
Genetic and phenotypic landscape of the major histocompatibilty complex region in the Japanese population
2019
Overview
To perform detailed fine-mapping of the major-histocompatibility-complex region, we conducted next-generation sequencing (NGS)-based typing of the 33 human leukocyte antigen (HLA) genes in 1,120 individuals of Japanese ancestry, providing a high-resolution allele catalog and linkage-disequilibrium structure of both classical and nonclassical HLA genes. Together with population-specific deep-whole-genome-sequencing data (
n
= 1,276), we conducted NGS-based HLA, single-nucleotide-variant and indel imputation of large-scale genome-wide-association-study data from 166,190 Japanese individuals. A phenome-wide association study assessing 106 clinical phenotypes identified abundant, significant genotype–phenotype associations across 52 phenotypes. Fine-mapping highlighted multiple association patterns conferring independent risks from classical HLA genes. Region-wide heritability estimates and genetic-correlation network analysis elucidated the polygenic architecture shared across the phenotypes.
Sequencing of the MHC region in the Japanese population provides insight into population-specific allelic and structural variability. These data enable discovery and fine-mapping of genotype–phenotype associations across 52 phenotypes.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ 45/43
/ Alleles
/ Animal Genetics and Genomics
/ Antigens
/ Biomedical and Life Sciences
/ Disease
/ Genes
/ Genetic Association Studies - methods
/ Genome-wide association studies
/ Genome-Wide Association Study - methods
/ Genomes
/ Genomics
/ Genotype
/ Histocompatibility antigen HLA
/ Humans
/ Linkage Disequilibrium - genetics
/ Major Histocompatibility Complex - genetics
/ Mapping
/ Methods
/ Polymorphism, Single Nucleotide - genetics
/ Studies
